The present invention relates to the antibiotic nystatin (referred to in the older literature as fungicidin), and more specifically to a process for the purification of crude, partially purified or contaminated nystatin.
Nystatin and its method of preparation from Streptomyces noursei are disclosed by Hazen et al. in U.S. Pat. No. 2,797,183. Reference may also be made to Hazen and Brown, "Fungicidin, An Antibiotic Produced by a Soil Actinomycete," Proc. Soc. Exptl. Biol. Med. 76:93 (1950) and Brown, Hazen and Mason, "Effect of Fungicidin (nystatin) in Mice Injected with Lethal Mixtures of Aureomycin and Candida albicans," Science 117:609 (1953). The antibiotic is hereinafter referred to by the single term "nystatin".
Several methods for isolating nystatin from the fermentation media are known to the prior art. Examples of such processes are Hazen et al., U.S. Pat. Nos. 2,797,183; Vandeputte et al., 2,786,781; Vandeputte et al., 3,332,844; and Renella, 3,517,100. The nystatin isolated by known processes is not a highly purified, uniformly crystalline product. A method for obtaining nystatin in such a form is of course highly desirable, and several methods for achieving this result have been suggested by the prior art. For examples of such processes, reference may be made to Vandeputte, U.S. Pat. Nos. 2,832,719; Dutcher et al., 2,865,807; Mendelsohn, 3,509,255; Esse, 3,517,101; Keseleski et al., 3,911,113; and Metzger, 4,006,222.
British Pat. No. 809,105 deals with a process for water solubilizing amorphous nystatin, which comprises mixing the nystatin with an anionic surfactant, sodium lauryl sulfate being the most preferred.
U.S. Pat. No. 3,332,844 deals with a process for recovering nystatin from the fermentation broth in which it is produced. The process comprises extracting the wet mycelium in a medium comprising a lower alkanol, a mineral acid and an amine (the amine, which is preferably a tertiary amine, and the acid are preferably added together in the form of an acid-addition salt of the amine).
U.S. Pat. No. 4,006,222 deals with a process for the purification of nystatin in a lower alkanol system. The nystatin starting material is purified by first suspending it in a lower alkanol, solubilizing the nystatin with a weak organic acid, filtering off the lower alkanol extract, combining a chlorinated hydrocarbon solvent and the lower alkanol extract, neutralizing the resultant mixture, and precipitating purified nystatin by the addition of water.